Anti-integrins as a potential therapeutic target in angiogenesis

Several physiological processes including cell activation, migration, proli feration and differentiation require direct contact between cells or extrac ellular matrix (ECM) proteins. Cell-cell and cell-matrix interactions are m ediated through several different families of cell adhesion molecules (CAMs ), including the selectins, the integrins, the cadherins and the immunoglob ulins. Newly discovered CAMs, along with the discovery of new roles of inte grins, selectins and immunoglobulins in certain disease states, provide a g reat opportunity to develop therapeutic, and perhaps diagnostic, modalities . CAMs play a very significant and critical role in both normal and pathophys iological disease states. For this key reason, the selection of specific an d relevant CAMs to target certain disease conditions, without interfering w ith other normal cellular functions is a very important prerequisite for th e ultimate success in developing truly active and safe therapeutic strategi es. Recent breakthroughs with animal models, the latest advances in the und erstanding of the signalling pathways, transcriptional regulation and the s tructure/function aspects of CAMs, the role of CAMs and ECM proteins in cel lular migration, spreading, proliferation and survival illustrate the poten tial impact of using CAMs as a novel strategy. Exciting advances in our und erstanding of several CAMs, most notably the alpha v beta 3, alpha v beta 5 , alpha 4 beta 1, alpha 5 beta 1 and alpha IIb/beta 3 integrin receptors, a nd their direct relationships to different disease states represent a treme ndous therapeutic and diagnostic opportunity. The role of CAMs and ECM proteins in various pathological processes (includ ing angiogenesis, thrombosis, apoptosis, cell migration and proliferation) leading to both acute and chronic disease states, (such as ocular diseases, metastasis, unstable angina, myocardial infarction, stroke, osteoporosis, a wide range of inflammatory diseases, vascular remodelling and neurodegene rative disorders) have been recently documented. One key success in this fi eld is evidenced by the potential role of the platelet GPIIb/IIIa integrin in the prevention, treatment and diagnosis of various thromboembolic disord ers. The discovery of various therapeutic candidates based on the key role of alpha v (alpha v beta 3 and alpha v beta 5) and alpha 5 beta 1 integrins in angiogenesis will be the focus of this review.